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Lecture 18 - Chemical Methods - Suppress Cell Wall Synthesis and Antimetabolites
Suppression of cell wall synthesis will work better on cells that are synthesizing cell wall, or younger cells, but still work on older bacteria. Penicillins Penicillins are chemicals extracted from the penicilliium mold, and then sometimes modified. They are effective against Group A Streptococcus (pyogenes), Clostridium perfringens, Neisseria meningitidis, and Treponema pallidum. Natural Penicillins Natural Penicillins include Benzyl penicillin (Penicillin G'''), which is given by IV because it is sensitive to stomach acid, and '''Phenoxymethyl penicillin (Penicillin V'''), which is resistant to stomach acid and is taken orally. '''Repository Penicillins Penicillin G can be mixed with benzathine to slow down the release of the penicillin, yielding Benzathine Penicillin G. This compound can be used as a prophylactic for rheumatic fever, caused by Streptococcus. It can also be used as a treatment for Treponema pallidum (syphilis). Semi-Synthetic Penicillins Ampicillin have an extra amino group which allows it to permeate the outer membrane of Gram-negative bacteria, which makes it broad spectrum. It is a drug of choice for UTIs caused by Proteus mirabilis. Amoxycillin have an extra hydroxyl group, which also makes it a broad spectrum drug. Functionally very similar to Ampicillin. Ticarcillin have an extra sulfur ring and is used as a drug of choice for Pseudomonas other infections (lungs or bones), not for UTIs. Beta Lactamase Resistant Penicillins Methicillin have a modified side chains which makes it resistant to penicillinase. MSSA is sensitive to methicillin even though it has penicillinase. However, MRSA is resistant to methicillin due to its penicillin-binding proteins even though it has penicillinase. Oxacillin is given by either IV or IM and is used for systemic infections. Augmentin "augments" oxacillin with potassium clavulanate, which is a suicide inhibitor for penicillinase. This extends the activity of the oxacillin in MSSA strains. Multiple Drug Resistant Staphylococcus aureus (MDRSA) is resistant to multiple drugs including Streptomycin due to efflux pumps. Other that Suppress Cell Wall Synthesis 'Cephalosporins' This compound look like penicillins but with two side groups. They come from Cephalosporium molds, and are used as a substitute for penicillin in patients who are allergic to penicillin. The drug is broken down by cephalosporinase instead of penicillinase. There are 5 generations of this drug: #'Cephalexin' (Keflex) is the first generation of cephalosporins. They are narrow-spectrum and still used for staph and strep. It is used for treatment and as a prophylactic #'Cefotiam' is the second generation, and shows more activity against Gram-negatives such as Enterobacter, Proteus, Haemophilus. #'Ceftriaxone' and Cefotaxime are the third generation and are used as the drug of choice for Gram-negative infections such as Klebsiella pneumoniae. #'Cefepime' are the fourth generation and are also used as a DOC 'for Gram-negative infections. #'Ceftaroline is the fifth generation and is used to treat community-acquired bacterial pneumonia (CABP) 'Carbapenems' Carbapenems are β-lactam antibiotics that are also a broad-spectrum drug. Their structure that differs from the penicillin renders them highly resistant to most β-lactamases. They are effective and used as a last resort against Acinetobacter in order to avoid developing resistance in bacteria. Primaxin '''is a combination of the imipenem and a cilastatin. Imipenem is a specific carbapenem drug, and cilastatin is a renal dipeptidase inhibitor that blocks '''dehydropeptidase I, which would break down the imipenem into a neurotoxic metabolite. 'Bacitracin' Bacitracin is a narrow-spectrum drug that is secreted by Bacillus bacteria that are effective in treating gram-positive infections. This is part of the triple-antibiotic ointment. 'Vancomycin' This was known as the most powerful antibiotic for Gram-positive species that are the DOC for MRSA. Used as a last resort because it is very toxic and can lead to resistance. VRE (vancomycin-resistant Enterococci) can kill people with diarrhea. Antimetabolites Antimetabolites are mostly just competitive inhibitors for bacterial enzymes. Specifically, bacteria break down PABA (para-amino benzoic acid) into folic acid through a series of metabolic pathways. Folic acid is used in the synthesis of bacterial DNA, and therefore antimetabolites are usually not cital but rather static or inhibitory. Sulfa drugs Sulfonamides (sulfa drugs) contain a benzene group and an amino group, similar to PABA. The work at the first step in the PABA pathway. 'Sulfadiazine' Sulfadiazine is a sulfa drug that is used along with silver in dressings for burn victims. It is used with silver to increase effectiveness and leave no resistant bacteria behind. 'Bactrim' Bactrim is a mixture of sulfamethoxazole and trimethoprim that have synergistic action. The sulfamethoxazole is the sulfa drug in this combination. This is used to treat uncomplicated urinary tract infections coli from thongs and shitty wiping, which occur with no antibiotics, instrumentation, or obstructions. Bactrim is also used to treat Pneumocystis (previously carinii) jiroveci pneumonia (PCP). 'Sulfones' Sulfones, not to be confused with sulfonamides, have a sulfur double bonded to two oxygens, though they also inhibit dihydropteroate synthase like sulfa drugs. 'Dapsone' Dapsone is a sulfone that is used as a drug of choice for Mycobacterium Leprae.' Not a sulfa drug'. 'Isoniazid ' Also called INH, and isonicotinic hydrazide, isoniazid is used as a DOC for tuberculosis. The mode of action is probably an antometabolite; the medical community is not sure. When treated with this drug, TB bacteria show decreased amounts of mycolic acid in their cell wall. '**PAS' P-aminosalicylic acid, or PAS for short, is used to treat multiple drug-resistant (MDR) tuberculosis, which are resistant to both INH and rifampim. It is also used to treat XDR TB, which is extensively resistant, and is defined to be resistant to INH, Rifampim, any fluroquinoline (cyprofloxacin), and at least one injectable aminoglycoside (amikacin, kanamycin, or capreomycin). pH Metabolism can also be hindered by pH. Enzymes in food vacuoles require a certain pH to work. Quinine, chloroquine, and primaquine are alkaline and used for treatment against Malaria. They make the pH of the blood too basic for the hemepolymerase to break down heme, which builds up to an amount that kills the protist. Quinine is also present in tonic water.